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Lymphogenic metastatic spread of auricular VX2 carcinoma in New Zealand white rabbits.

INTRODUCTION: The auricular VX2 carcinoma of the New Zealand white rabbit serves as an animal model for human squamous cell carcinomas of the head and neck region (HNSCC), since both tumors tend to metastasize lymphatically, leading to early lymph node and subsequent distant metastasis. The aim of this study was to examine the pattern of lymphogenic metastatic spread in untreated auricular VX2 carcinomas, since the resulting knowledge potentially could help in the development of new treatment strategies for human HNSCC. MATERIALS AND METHODS: VX2 carcinomas were implanted into both ears of 22 New Zealand white rabbits. The animals were sacrificed at days 7, 14, 21, 28 or 32 after tumor implantation, followed by a detailed histopathological examination of their head and neck lymph nodes. RESULTS: On day 7 after tumor implantation 25% of the animals had metastases in the parotid lymph node, which is the first draining lymph node of the tumor region. This number rose to 87.5% by day 28. At this time 12.5% of all animals also had an additional metastasis in the second echelon node. CONCLUSION: A reproducible metastatic spread into the first draining lymph node could be demonstrated for the auricular VX2 carcinoma of the New Zealand white rabbit. The VX2 carcinoma therefore appears to be a highly suitable animal model for studying the sentinel node concept in the context of human HNSCC.

Animals↗

Deoxyribonucleic acid flow cytometry on primary adenocarcinoma of the bladder: an analysis of 36 cases.

Deoxyribonucleic acid flow cytometry was applied retrospectively to 36 primary pure adenocarcinomas of the bladder, stages A through D. Six tumors were enteric, 3 mucinous, 11 signet ring, 3 papillary, 5 unspecified and 8 mixed. Eight tumors were urachal in origin and 28 were nonurachal. The deoxyribonucleic acid pattern was diploid in 12 cases, aneuploid in 19, tetraploid in 3 and uncertain in 2. Nineteen patients died of disease after a mean of 27.4 months, 7 were well at a mean of 73.9 months, 8 had died of an unrelated cause and 1 was alive with metastatic disease. Ploidy pattern did not correlate with tumor stage, histological pattern or type of outcome: 6 of 12 patients with diploid and 12 of 22 with nondiploid tumors died of disease. However, if the tumor was urachal 1 of 4 patients with a diploid pattern died of disease, while 3 of 4 with an aneuploid pattern either died or were alive with disease. Our data suggest that deoxyribonucleic acid ploidy pattern apparently is not a significant predictor of outcome for primary adenocarcinoma of the bladder except possibly when the origin is urachal.

Adenocarcinoma↗

Tumor cell plasticity in uveal melanoma: microenvironment directed dampening of the invasive and metastatic genotype and phenotype accompanies the generation of vasculogenic mimicry patterns.

The histological detection of laminin-rich vasculogenic mimicry patterns in human primary uveal melanomas is associated with death from metastases. We therefore hypothesized that highly invasive uveal melanoma cells forming vasculogenic mimicry patterns after exposure to a laminin-rich three-dimensional microenvironment would differentially express genes associated with invasive and metastatic behavior. However, we discovered that genes associated with differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21) were up-regulated in highly invasive uveal melanoma cells forming vasculogenic mimicry patterns, and genes associated with promotion of invasive and metastatic behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2 (chondroitin sulfate proteoglycan; versican) were down-regulated. After forming vasculogenic mimicry patterns, uveal melanoma cells invaded only short distances, failed to replicate, and changed morphologically from the invasive epithelioid to the indolent spindle A phenotype. In human tissue samples, uveal melanoma cells within vasculogenic mimicry patterns assumed the spindle A morphology, and the expression of Ki67 was significantly reduced in adjacent melanoma cells. Thus, the generation of vasculogenic mimicry patterns is accompanied by dampening of the invasive and metastatic uveal melanoma genotype and phenotype and underscores the plasticity of these cells in response to cues from the microenvironment.

Biomarkers, Tumor↗

Staging, growth properties and metastatic behaviour of a transplantable murine T-cell lymphoma.

Cell surface markers, enzymatic patterns, proliferation characteristics and metastatic behaviour of the DSA/2 derived SL2 lymphoma were determined. SL2 cells are sensitive to a heterologous antiserum to murine T-cells and to allo-antisera for Thy 1.2 and TL 1.2.3. They show acid-phosphatase, betaglucuronidase, acid-alpha-naphthytesterase and non-specific esterase staining. The reactions for ATP-ase, and 5'nucleotidase were negative. The SL2 tumour cells can be transplanted in vivo, growing rapidly both as an ascites or a solid tumour, and can be grown in vitro as a suspension culture (doubling time about 18 hours). One hundred cells kill an animal after i.p. transplantation, while 1,000 cells kill an animal after s.c. transplantation. Histopathological examination combined with TEM shows that SL2 metastasizes rapidly, especially after i.p. injection. The metastasizing cells reach the blood vessels in the lung septa and extravascular positions in the liver.

Animals↗

Adenocarcinomas metastatic to the liver: the value of cytokeratins 20 and 7 in the search for unknown primary tumors.

BACKGROUND: Metastatic adenocarcinoma in the liver with an unidentified primary tumor site is a common clinical problem. Pathologists often are asked to identify the primary tumor site. The histologic picture itself usually is not helpful, because the histology may be similar in the metastases of tumors with different primary localizations. Immunohistochemistry can be helpful, but the previously recommended antibody panels are too complicated for everyday use. METHODS: A simple immunohistochemical algorithm with two monoclonal cytokeratin (CK) antibodies, CK20 and CK7, was tested on 93 autopsy cases of adenocarcinomas metastatic to the liver. Sections of the liver metastases were stained automatically and evaluated as negative (no staining), focally positive, or diffusely positive. Statistical comparison of the staining results for a single antibody was calculated as an odds ratio. RESULTS: Thirty-six of 93 (39%) metastases proved to be CK20 positive (+). In this group, the CK20+/CK7 negative (-) pattern was highly characteristic for colorectal localization of the primary tumor, having been observed 17 of 21 of the cases (81%). The CK20+/CK7+ pattern of the metastatic liver adenocarcinomas was highly suggestive of primary localization in the pancreas or biliary tract (11 of 14 cases; 79%). Exclusion of the tumors originating in the stomach raised these values to 94% and 92%, respectively. The statistically calculated predicted probability of primary tumor site being in the colon or rectum for CK20+/CK7- metastasis was 78,41%, the probability of a primary tumor being located in the pancreas or biliary tract was 74,85%, if calculated for the whole study group. CONCLUSIONS: The tested simple algorithm proved to be useful in CK20 positive (+) cases, predicting a primary tumor localization in the colon, rectum, pancreas, or biliary tract with high accuracy. The CK20- group was too heterogeneous to be classified adequately by these two antibodies.

Adenocarcinoma↗

Comparative immunohistochemical study of primary and metastatic carcinomas of the liver.

Distinguishing primary hepatocellular carcinoma (HCC) from metastatic carcinomas to the liver is often difficult, if not impossible, particularly in needle biopsy and fine-needle aspiration specimens. In an attempt to identify a specific immunohistochemical profile that would distinguish HCC from metastatic carcinomas, we studied 56 HCCs, 8 cholangiocarcinomas, and 24 metastatic adenocarcinomas with monoclonal antibodies to alpha-fetoprotein (AFP), keratin (AE1, AE3, and CAM5.2), Leu-M1, human milk fat globule (HMFG-2), tumor-associated glycoprotein-72(B72.3), epithelial specific membrane antigen (Ber-EP4), and BCA-225 (CU-18). Both monoclonal and polyclonal (mCEA and pCEA) antibodies to carcinoembryonic antigen also were used. Metastatic adenocarcinomas were often positive for CU-18(71%), Leu-M1 (75%), B72.3 (50%), HMFG-2 (67%), Ber-EP4(83%) and mCEA(71%). Using these antibodies, the frequency of positivity for HCC was 9%, 16%, 11%, 20%, 36%, and 11%, respectively. CU-18 was the only monoclonal antibody in which there was a significant difference in positive rates between HCC and metastatic adenocarcinomas. Most HCCs (71%) revealed a bile canalicular staining pattern with pCEA. Because this staining pattern was absent in metastatic carcinomas, pCEA appears to be useful in confirming a diagnosis of HCC. AE1, AE3 and CAM5.2 antibodies were not useful in distinguishing HCC from metastatic carcinomas. Each cholangiocarcinoma shared a staining profile similar to that of metastatic carcinomas.

Adenocarcinoma↗

Primary dermal melanoma: a distinct subtype of melanoma.

BACKGROUND: The term primary dermal melanoma has been used to describe a subtype of melanoma confined to the dermis and/or subcutaneous fat that histologically simulates metastasis but is associated with an unexpectedly prolonged survival. We report 7 cases of primary dermal melanoma diagnosed from 1998 to 2002 with no identifiable junctional or epidermal component or nevoid precursor. Histopathologic and immunohistochemical features were compared with known cases of cutaneous metastasis and nodular melanoma in an attempt to differentiate this entity from clinical and pathologic mimics. OBSERVATIONS: Seven patients had a single dermal and/or subcutaneous focus of melanoma. Metastatic staging workup findings were negative, including results from sentinel node and imaging studies. Mean Breslow depth was 7.0 mm, and mean maximum tumor diameter was 6.2 mm. The study cohort showed 100% survival at mean follow-up of 41 months (range, 10-64 months). Immunohistochemical analysis with S100, HMB-45, Ki-67, CD34, and p75 antibodies showed no significant staining patterns compared with metastatic and nodular melanomas. CONCLUSIONS: Primary dermal melanoma appears to be a distinct subtype of melanoma based on the excellent prognosis associated with this case series and others. Additional research focusing on cause, appropriate staging, and outcome of previously identified solitary dermal metastasis is warranted to further delineate this entity.

Adult↗

Geographic disparities in diagnostic screening for metastatic uveal melanoma.

PURPOSE: To evaluate current practice patterns in diagnostic screening for asymptomatic metastatic uveal melanoma. DESIGN: Survey. PARTICIPANTS: Ocular oncologists practicing in North America (United States, Canada) and Europe. METHODS: Questionnaire sent to specialists participating in the Collaborative Ocular Melanoma Study (COMS) or listed in the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer. MAIN OUTCOME MEASURES: Methods used to screen patients with uveal melanoma for asymptomatic metastasis at initial presentation and follow-up. RESULTS: Thirty-six of 43 (84%) North American (COMS) specialists and 57 of 103 (55%) European specialists responded to the survey. At presentation, 6 of 36 (17%) North American specialists, versus 54 of 57 (95%) European specialists, performed at least one type of liver imaging study (computed tomography, magnetic resonance imaging, ultrasonography, or nuclear medicine) (P<0.0001). On follow-up, only 1 of 36 (3%) North American specialists, versus 45 of 57 (79%) European specialists, obtained a liver imaging study (P<0.0001). Thirty-six of 36 (100%) North American specialists, versus 49 of 57 (86%) European specialists, ordered chest x-rays at presentation (P<0.02). This disparity was greater at the time of follow-up, when 28 of 36 (78%) North American specialists, versus 28 of 57 (49%) European specialists, ordered chest x-rays (P<0.01). Similar proportions of specialists in North America and Europe obtained a physical examination and liver function tests at the time of presentation and on subsequent follow-up examination. CONCLUSIONS: Significant differences exist between ocular oncologists in North America and Europe in the use of techniques to screen for metastatic uveal melanoma. North American COMS centers rely primarily upon liver function tests and chest x-rays. The majority of European centers use liver ultrasonography at initial diagnosis and continue to do so every 6 months. Cost-effective screening protocols for patients with uveal melanoma should be designed and implemented uniformly among ocular oncologists.

Europe↗

Nuclear overexpression of bcl-2 oncoprotein during the progression of human stomach cancer.

We unexpectedly observed strong nuclear overexpression of bcl-2 protein in advanced stomach cancer. As far as we know, such expression has not yet been reported. To investigate the significance of nuclear expression of bcl-2 protein in gastric carcinoma, we immunohistochemically analyzed bcl-2 overexpression in a gastric carcinogenic sequence, including 19 tubular adenomas (TA), 20 early carcinomas (EGC), and 20 advanced carcinomas (AGC). While TA displayed a specific granular and supranuclear cytoplasmic staining pattern, adenocarcinomas showed a strong nuclear staining pattern. Nuclear staining of bcl-2 was observed in 50% of AGC, 30% of EGC, and 10% of TA; cytoplasmic staining, on the other hand, was observed in all TA, 5% of EGC, and 10% of AGC. Nuclear bcl-2 overexpression differed according to the histologic type of AGC, occurring in 67% of the diffuse type and 25% of the moderately-to-well differentiated type. In the diffuse type, nuclear bcl-2 positive AGC predominated. In metastatic lesions, the pattern of bcl-2 immunostaining was almost identical to that seen in primary tumor. These results suggest that nuclear expression of bcl-2 may be related to malignant transformation in the stomach and is frequently associated with diffuse type advanced gastric adenocarcinomas.

Adenoma↗

Cytokeratin 7 and 20 staining for the diagnosis of lung and colorectal adenocarcinoma.

The origin of metastatic adenocarcinoma lesions can sometimes be difficult to diagnose. The objectives of our study were to establish the cytokeratin staining pattern of primary and metastatic lung and colorectal adenocarcinomas, and to determine if this helps to identify the site of origin of metastatic lesions. We reviewed a total of 102 tissue samples from patients in our tumour registry, with either primary or metastatic lung or colorectal adenocarcinoma. Tissue sections were stained for cytokeratin 7 and 20 and read as positive or negative for staining. Clinical and radiologic information was reviewed from computerised charts. The cytokeratin 7+/cytokeratin 20- pattern characterised 96% (29 out of 30) of primary and 95% (21 out of 22) of metastatic lung adenocarcinomas. All the primary (26), and 88% (21 out of 24) of metastatic colorectal adenocarcinomas stained cytokeratin 7-/cytokeratin 20+. Samples from a variety of metastatic sites were evaluated for cytokeratin 7 and 20 staining. Out of the 102 samples, in 95% (97 out of 102) of the cases, the cytokeratin 7 and cytokeratin 20 staining pattern characterised and differentiated between lung and colorectal adenocarcinoma. Primary and metastatic lung adenocarcinomas show a cytokeratin 7+/cytokeratin 20- staining pattern, while colorectal adenocarcinomas stain cytokeratin 7-/cytokeratin 20+. Cytokeratin staining is helpful in the diagnostic differentiation of metastatic lesions from these two common primaries, and assists in determining the site of origin of metastatic lesions.

Adenocarcinoma↗

Pattern of failure and survival of patients with metastatic urothelial tumors relapsing after cis-platinum-based chemotherapy.

Cis-platinum-based chemotherapy combinations have improved the outcome of patients with metastatic urothelial tumors, since two-thirds of these patients respond to treatment. Nevertheless, the majority of such patients have relapse within a median of 12 months. To define the pattern of failure and subsequent outcome, we retrospectively assessed 58 consecutive patients with relapse after prior response to cis-platinum-based combination chemotherapy. Of the patients who presented initially with local-regional metastases, 74% had relapse with involvement of a similar site, while only 26% of these patients had visceral metastases at relapse. The median survival after relapse was 9 months, and parameters associated with longer survival were local-regional relapse (10.7 months) and response to salvage chemotherapy (12.6 months). These data suggest that select patients with urothelial tumors and local-regional metastases may benefit from consolidation therapy with surgery or radiotherapy after maximum response to chemotherapy.

Adult↗

Effect of retinoic acid on morphological changes of human pancreatic cancer cells on collagen gels: a possible association with the metastatic potentials.

Pancreatic carcinoma is an invasive and metastasizing type of malignancy. We established six pancreatic cancer cell lines from human pancreatic carcinomas, three highly metastatic lines (KP-1NL, KP-4, and SUIT-2) and three minimally metastatic lines (KP-2, KP-3, and BxPC-3). The three highly metastatic cell lines grew in a fibroblastoid pattern on collagen gels, whereas the three minimally metastatic cell lines grew in an epithelioid pattern under similar conditions. Western blot and Northern blot analyses indicated much higher levels of E-cadherin in the three minimally metastatic cell lines relative to the three highly metastatic cell lines. When the effect of all-trans-retinoic acid on the growth patterns of the three highly metastatic lines was examined, we observed a dramatic change from fibroblastoid to epithelioid growth in SUIT-2 cells. Although all six cell lines had comparable levels of retinoic acid receptor-gamma, retinoic acid receptor-beta was expressed only in SUIT-2 cells. Treating SUIT-2 cells with retinoic acid also induced the upregulation of E-cadherin expression. When SUIT-2 cells were treated with retinoic acid receptor-specific agonists, 13-cis-retinoic acid and Am555S, a morphological change from fibroblastoid to epithelioid growth was induced. Retinoic acid receptor-specific antagonists, LE135 and LE540, inhibited retinoic acid-induced change of the growth patterns. The effect of retinoic acid and its derivatives on the growth pattern was discussed in a possible association with their antimetastatic activities of pancreatic cancer.

Cadherins↗

Metastatic inefficiency: the scientific basis for resection of liver metastases from colorectal cancer.

Hematogenous metastases from primary colon or rectal cancer develop in a definite step-wise fashion. In most patients the primary tumor disseminates to local lymph nodes, to the liver, or to peritoneal surfaces. Lung metastases only develop after considerable progression of the secondary tumor deposits in liver or in lymph nodes. This is considered a metachronous or step-wise progression of the malignant process. Only in a minority of patients is there synchronous spread of the malignancy from the primary site to systemic sites. The dissemination of colorectal malignancy is in great contrast to the dissemination of other malignancies such as breast cancer or melanoma. Considerable autopsy and laboratory data support the metachronous pattern of dissemination. Metastatic inefficiency (overt destruction of a majority of tumor cells within blood vessels or lymphatic channels) explains the preponderance of metastatic deposits in the first capillary bed or first lymphatic network draining a primary colorectal malignancy. These observations constitute the scientific basis for resection of liver metastases from colorectal cancer and the large proportion of patients who can be cured by the surgical resection of one or a few liver metastases.

Colonic Neoplasms↗

[A study of DNA ploidy patterns of gastric cancers].

The nuclear DNA fluorescence of gastric cancer cells which were obtained from endoscopic biopsies and paraffin block specimen was measured. Histograms in 142 cases could be roughly classified into four types: Type Ia, means diploid pattern without polyploid cells, type Ib, diploid pattern with polyploid cells, type II, heteroploid pattern and type III, mosaic pattern. Although these DNA patterns showed no correlation with histological types, type Ia was frequently found in early-stage cancer and type III in advanced-stage cancer. In cases without vascular invasion and in each metastasis, type Ia were significantly numerous. With regard to prognosis, the survival rate was becoming poorer in order of Ia less than Ib less than II less than III. In 41 cases out of 45 advanced-stage cancers, DNA patterns of superficial and deep portion of gastric cancer were found the same. In 5 cases, DNA patterns of cancer cells in metastatic lymph nodes were coincident with DNA patterns in gastric cancers. These results suggested that the measurement of nuclear DNA pattern may provides a biological activity of gastric cancer cells and preoperative examination of endoscopic biopsy specimens from this aspect is also clinically important.

Adenocarcinoma↗

Spread of prostate carcinoma to the perirectal lymph node basin: analysis of 112 rectal resections over a 10-year span for primary rectal adenocarcinoma.

We recently identified metastatic prostate carcinoma (PCA) within perirectal lymph nodes (PLNs) from 2 patients undergoing abdominoperineal resection (APR) for rectal adenocarcinoma (RA). As this phenomenon has not been addressed by any studies in the literature and because these positive PLNs had the potential to be mistakenly diagnosed as metastatic RA, we were prompted to undertake a retrospective study of rectal resections for RA to determine the frequency of PCA metastasizing to the PLNs in this patient population. The laboratory information system of the Department of Pathology, Capital Health, Halifax, Nova Scotia was searched for lymph node (LN)-positive RAs resected by low anterior resection or APR in male patients between January 1, 1992 and December 31, 2002. The hematoxylin and eosin slides were retrieved and reviewed, comparing the histology of the primary rectal tumor with that of the LN metastases in each case. Metastases having a different histologic appearance than the primary rectal tumor or having a pattern suggestive of metastatic PCA were analyzed by immunohistochemistry to detect prostate specific antigen (PSA), prostatic acid phosphatase (PAP), cytokeratin 7 (CK7), cytokeratin 20 (CK20), and carcinoembryonic antigen in LN metastases and in each RA. The presence or absence of mucin in the tumors was assessed by staining with Alcian blue, periodic acid-Schiff (PAS) +/- diastase, and modified PANFOPAS (2-hydroxy-3-naphthoic acid hydrazide/fast black B/saponification/periodic acid-Schiff). The study identified 112 cases of RA with positive LNs. Of those, 5 of 112 (4.5%) were identified as having metastatic PCA within the PLNs. All five were positive for PSA and PAP and only one case had rare CK20-positive tumor cells. The primary RAs were all diffusely positive for CK20 and carcinoembryonic antigen. Two cases of metastatic PCA expressed colonic type/acetylsialomucin, which was also seen in well-differentiated primary RAs. These 5 patients had a mean age of 76.8 years (range, 68-82 years). Four (80%) underwent APR while one (20%) underwent a low anterior resection. The mean number of LNs identified per case was 14 (range, 5-26). The mean number of LNs per case with metastatic PCA was 7.6 (range, 1-18). The majority of the LNs were under 1.0 cm in diameter. Two cases (40%) were associated with significant extranodal extension of PCA. The PLNs were mistakenly diagnosed as being involved by RA 40% of the time. On follow-up, 2 patients (40%) had died with progressive pelvic tumor, while 3 patients (60%) were alive, including 2 who, as a result of the study, were referred to the urology service for management. Both of these patients were subsequently started on medical (anti-androgen) therapy and 1 additionally had bilateral orchiectomy. In 4 of the patients, the serum PSA after the rectal resection ranged from 2.5 to 13.5 ng/mL. In 1 patient, the serum PSA was markedly elevated (5961 ng/mL), and this patient was subsequently identified on bone scan as having extensive skeletal metastases. This study identified a subset (4.5%) of patients with RA and PLNs positive for PCA. PCA may extend to the PLN basin and therefore influence the management of patients with rectal tumors and the staging, LN dissection, and management of patients with PCA. Moreover, the LNs were incorrectly diagnosed as metastatic RA 40% of the time, emphasizing the need to consider the differential diagnosis of metastatic PCA when evaluating PLNs. The diagnosis of metastatic PCA can be confirmed using an immunohistochemical panel consisting of PSA, PAP, CK20, and carcinoembryonic antigen along with mucin stains in some cases. In patients undergoing APR for RA, there should be preoperative screening for PCA as it will not be possible to do a digital rectal examination or transrectal ultrasound post-APR, and a prostate biopsy, if necessary, would have to be done via the more difficult transperineal approach.

Adenocarcinoma↗

Histopathologic aspects of cutaneous metastatic disease.

In cutaneous metastatic disease the histologic pattern may be specific or nonspecific. Carcinoma cutis most often shows only the nonspecific pattern of an adenocarcinoma, a squamous cell carcinoma, or an undifferentiated metastatic tumor. However, certain clinical and histologic characteristics may suggest a primary tumor site and type. In addition, special histologic stains and the use of immunohistochemical and electronmicroscopic techniques may also prove valuable in the diagnosis of carcinoma cutis and other cutaneous metastatic diseases.

Adenocarcinoma↗

Epidermal growth factor receptor overexpression and genetic aberrations in metastatic squamous-cell carcinoma of the skin.

BACKGROUND: Cutaneous squamous-cell carcinoma (SCC) sometimes causes lymph node metastasis and results in poor prognosis. However, little is known about cytogenetic alterations underlying tumor progression or metastasis. The aim of the present study was to investigate the genetic aberrations and expression of epidermal growth factor receptor (EGFR) in metastatic SCC of the skin. METHODS: We undertook comparative genomic hybridization (CGH) analysis of 4 specimens which were obtained from a case of cutaneous SCC, including the primary lesion and 3 lymph nodes of the metastatic lesion. RESULTS: Only one amplified locus (7p12-13) was detected in any metastatic lymph node, in which the EGFR gene is located. Therefore, we applied immunohistochemistry for EGFR to 5 cases of metastatic SCC including the case analyzed using CGH and 4 other cases (5 primary and 5 metastatic lesions). EGFR was expressed in 4 of 5 cases (both primary and metastatic lesions, including the case analyzed using CGH), and the staining patterns of primary and metastatic lesions were different. The primary tumors were focally weakly positive for immunostaining (+), whereas the 4 metastases were diffusely and strongly positive (+++). CONCLUSIONS: Our findings suggest that the clone with EGFR expression might selectively metastasize in some cutaneous SCCs. The existence of an EGFR-negative case reveals that EGFR expression is not always required for skin carcinogenesis, but expression of EGFR might confer metastatic potential of cutaneous SCCs.

Carcinoma, Squamous Cell↗

Cytologic features of metastatic nasopharyngeal carcinoma.

The aim of the study was to describe the cytologic features of metastatic nasopharyngeal carcinomas (NPC) to lymph node, which would help in arriving at a definite diagnosis, particularly in cases of occult primary with predominant finding of cervical lymphadenopathy. This is a retrospective study over a period of 2 yr (January 2000 to December 2001) and included 15 cases of NPC metastasizing to cervical lymph nodes. All cases had histopathologic diagnosis of primary NPC. Two independent observers studied detailed cytomorphology of these cases. The FNAC smears were cellular and except for three cases revealed predominantly discohesive malignant cells admixed with lymphocytes. Cellular degeneration and naked tumor cell nuclear were seen in all cases. The tumor cells showed mild to moderate nuclear pleomorphism, vesicular chromatin, and scanty cytoplasm with ill-defined cytoplasmic borders. All 15 cases were typed according to the World Health Organization (WHO) classification as types I, II, and III NPCs. There were two cases of type I NPCs, five cases of type II, and eight cases of type III pattern. FNAC of metastatic NPC in lymph node is a valuable diagnostic modality in suggesting the site of origin of the tumor. Furthermore, it is also helpful to exclude residual disease and recurrence in a treated patient with lymphadenopathy.

Adolescent↗